Fas/CD95 Deficiency in ApcMin/+ Mice Increases Intestinal Tumor Burden

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2010 Feb 9

PMID 20140201

Citations 19

Authors

Hector Guillen-Ahlers

Mark A Suckow

Francis J Castellino

Victoria A Ploplis

Affiliations

Soon will be listed here.

Abstract

Background: Fas, a member of the tumor necrosis family, is responsible for initiating the apoptotic pathway when bound to its ligand, Fas-L. Defects in the Fas-mediated apoptotic pathway have been reported in colorectal cancer.

Methodology/principal Findings: In the present study, a variant of the Apc(Min/+) mouse, a model for the human condition, Familial Adenomatous Polyposis (FAP), was generated with an additional deficiency of Fas (Apc(Min/+)/Fas(lpr)) by cross-breeding Apc(Min/+) mice with Fas deficient (Fas(lpr)) mice. One of the main limitations of the Apc(Min/+) mouse model is that it only develops benign polyps. However, Apc(Min/+)/Fas(lpr) mice presented with a dramatic increase in tumor burden relative to Apc(Min/+) mice and invasive lesions at advanced ages. Proliferation and apoptosis markers revealed an increase in cellular proliferation, but negligible changes in apoptosis, while p53 increased at early ages. Fas-L was lower in Apc(Min/+)/Fas(lpr) mice relative to Apc(Min/+) cohorts, which resulted in enhanced inflammation.

Conclusions/significance: This study demonstrated that imposition of a Fas deletion in an Apc(Min/+) background results in a more aggressive phenotype of the Apc(Min/+) mouse model, with more rapid development of invasive intestinal tumors and a decrease in Fas-L levels.

Citing Articles

FAS gene expression, prognostic significance and molecular interactions in lung cancer.

Li K, Tan S, Yang Z, Li C Front Oncol. 2024; 14:1473515.

PMID: 39416461 PMC: 11479862. DOI: 10.3389/fonc.2024.1473515.

Colorectal cancer murine models: Initiation to metastasis.

Pothuraju R, Khan I, Jain M, Bouvet M, Malafa M, Roy H Cancer Lett. 2024; 587:216704.

PMID: 38360138 PMC: 11257378. DOI: 10.1016/j.canlet.2024.216704.

Apoptotic cell death in disease-Current understanding of the NCCD 2023.

Vitale I, Pietrocola F, Guilbaud E, Aaronson S, Abrams J, Adam D Cell Death Differ. 2023; 30(5):1097-1154.

PMID: 37100955 PMC: 10130819. DOI: 10.1038/s41418-023-01153-w.

5-Fluorouracil Suppresses Colon Tumor through Activating the p53-Fas Pathway to Sensitize Myeloid-Derived Suppressor Cells to FasL Cytotoxic T Lymphocyte Cytotoxicity.

Yang Y, Zhang M, Zhang Y, Liu K, Lu C Cancers (Basel). 2023; 15(5).

PMID: 36900354 PMC: 10001142. DOI: 10.3390/cancers15051563.

Restoring FAS Expression via Lipid-Encapsulated FAS DNA Nanoparticle Delivery Is Sufficient to Suppress Colon Tumor Growth In Vivo.

Merting A, Poschel D, Lu C, Klement J, Yang D, Li H Cancers (Basel). 2022; 14(2).

PMID: 35053524 PMC: 8773494. DOI: 10.3390/cancers14020361.

References

Kinzler K, Vogelstein B . Lessons from hereditary colorectal cancer. Cell. 1996; 87(2):159-70. DOI: 10.1016/s0092-8674(00)81333-1. View

Burgering B, Coffer P . Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction. Nature. 1995; 376(6541):599-602. DOI: 10.1038/376599a0. View

Guillen-Ahlers H, Buechler S, Suckow M, Castellino F, Ploplis V . Sulindac treatment alters collagen and matrilysin expression in adenomas of ApcMin/+ mice. Carcinogenesis. 2008; 29(7):1421-7. PMC: 2899850. DOI: 10.1093/carcin/bgn123. View

Itoh N, Yonehara S, Ishii A, Yonehara M, Mizushima S, Sameshima M . The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell. 1991; 66(2):233-43. DOI: 10.1016/0092-8674(91)90614-5. View

Brunet A, Bonni A, Zigmond M, Lin M, Juo P, Hu L . Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell. 1999; 96(6):857-68. DOI: 10.1016/s0092-8674(00)80595-4. View

Kita H, Hikichi Y, Hikami K, Tsuneyama K, Cui Z, Osawa H . Differential gene expression between flat adenoma and normal mucosa in the colon in a microarray analysis. J Gastroenterol. 2006; 41(11):1053-63. DOI: 10.1007/s00535-006-1894-y. View

Suhara T, Kim H, Kirshenbaum L, Walsh K . Suppression of Akt signaling induces Fas ligand expression: involvement of caspase and Jun kinase activation in Akt-mediated Fas ligand regulation. Mol Cell Biol. 2002; 22(2):680-91. PMC: 139747. DOI: 10.1128/MCB.22.2.680-691.2002. View

Hohlbaum A, Moe S, Marshak-Rothstein A . Opposing effects of transmembrane and soluble Fas ligand expression on inflammation and tumor cell survival. J Exp Med. 2000; 191(7):1209-20. PMC: 2193164. DOI: 10.1084/jem.191.7.1209. View

Bedi A, Pasricha P, Akhtar A, Barber J, Bedi G, Giardiello F . Inhibition of apoptosis during development of colorectal cancer. Cancer Res. 1995; 55(9):1811-6. View

10.

Altomare D, Testa J . Perturbations of the AKT signaling pathway in human cancer. Oncogene. 2005; 24(50):7455-64. DOI: 10.1038/sj.onc.1209085. View

11.

OConnell J, Bennett M, Nally K, Houston A, OSullivan G, Shanahan F . Altered mechanisms of apoptosis in colon cancer: Fas resistance and counterattack in the tumor-immune conflict. Ann N Y Acad Sci. 2000; 910:178-92; discussion 193-5. DOI: 10.1111/j.1749-6632.2000.tb06708.x. View

12.

Green C, Liu T, Montel V, Hsiao G, Lester R, Subramaniam S . Chemoattractant signaling between tumor cells and macrophages regulates cancer cell migration, metastasis and neovascularization. PLoS One. 2009; 4(8):e6713. PMC: 2725301. DOI: 10.1371/journal.pone.0006713. View

13.

Lee S, Zhou T, Choi C, Wang Z, Benveniste E . Differential regulation and function of Fas expression on glial cells. J Immunol. 2000; 164(3):1277-85. DOI: 10.4049/jimmunol.164.3.1277. View

14.

Vaux D . Immunology. Ways around rejection. Nature. 1995; 377(6550):576-7. DOI: 10.1038/377576a0. View

15.

Suda T, Takahashi T, Golstein P, Nagata S . Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family. Cell. 1993; 75(6):1169-78. DOI: 10.1016/0092-8674(93)90326-l. View

16.

OConnor L, Harris A, Strasser A . CD95 (Fas/APO-1) and p53 signal apoptosis independently in diverse cell types. Cancer Res. 2000; 60(5):1217-20. View

17.

Seino K, Kayagaki N, Okumura K, Yagita H . Antitumor effect of locally produced CD95 ligand. Nat Med. 1997; 3(2):165-70. DOI: 10.1038/nm0297-165. View

18.

Su L, Kinzler K, Vogelstein B, Preisinger A, Moser A, Luongo C . Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene. Science. 1992; 256(5057):668-70. DOI: 10.1126/science.1350108. View

19.

Restifo N . Not so Fas: Re-evaluating the mechanisms of immune privilege and tumor escape. Nat Med. 2000; 6(5):493-5. PMC: 1955754. DOI: 10.1038/74955. View

20.

Ashkenazi A, Dixit V . Apoptosis control by death and decoy receptors. Curr Opin Cell Biol. 1999; 11(2):255-60. DOI: 10.1016/s0955-0674(99)80034-9. View